During the requested 5 years of additional support we wish to continue our work on a number of related projected to elucidate the hypothalamic control of prolactin (PRL), growth hormone (GH), thyrotropin (TSH) and adrenocorticotropin (ACTH). This area of research will involve the following specific aims: (1) action of brain peptides and other transmitters co-released into hypophysial portal vessels to alter release of these pituitary hormones by direct action on the adenohypophysis; (2) the actions of hypothalamic peptides to alter pituitary hormone release by effects on the hypothalamus as determined by in vivo and in vitro experiment; (3) further peptidergic systems in vivo and in vitro in the control of the release of the above hypothalamic peptides; (4) evaluation of the physiological significance of brain peptides in control of pituitary hormone release using antisera directed against the peptides or peptide antagonists; and (5) studies on receptors for brain peptides in the anterior pituitary gland. All of these studies will enhance our knowledge of the hypothalamic control of the adenohypophysis. They may also be therapeutic importance in treatment of endocrine diseases of metabolism. For instance, a peptide, such as galanin, which stimulated GH release by hypothalamic action might be therapeutically valuable in treatment of pituitary dwarfism.